The targeted and controlled delivery of small molecule therapeutics is an area of considerable current interest. The site-specific delivery of a therapeutic agent is a highly desirable feature for the treatment of many different conditions. In particular, products may be implanted in the body of humans or animals which contain therapeutics. However, there is a need to increase the efficacy and safety of such products.
One form of drug delivery involves the use of polymers to carry/retain the drug moiety to/at a specific location. Several approaches to this have been developed. Early controlled release methods involved drug-polymer formulations that released the drug upon breakdown of the polymer structure under physiological conditions, particularly through oral administration. Later developments included the preparation of drug-polymer systems based on admixing or on covalent linking.
The admixture approach involves the preparation of a polymer drug mixture that is then compounded into a solid device. The linking approach involves using drug molecules as monomers in formation of the polymer so that they form part of the polymer backbone, or covalently attaching drug molecules to a pre-formed polymer backbone. The linking approach gives rise to so called drug-polymer conjugate.
A major disadvantage of the admixture approach is that the release of the therapeutic agent is largely dependent on the breakdown of the polymer structure. This results in poor control of the rate of drug release with the possibility of uncontrolled dosages being delivered. Furthermore, the amount of drug that can be loaded into an admixture is limited (typically <10% by weight).
The linking approach also has a number of problems associated with it. Where the drug forms part of the polymer backbone, the polymer structure must degrade in order to release the drug. This will of course be disadvantageous where it is desirable to at least maintain the polymer structure while the drug is being released. Covalently attaching drug molecules to a pre-formed polymer backbone can also be problematic. In particular, steric and thermodynamic constraints can affect the amount of bioactive moiety that can be covalently attached, and also impact on the distribution of the bioactive moiety along the polymer backbone, which in turn can reduce control over the release of the bioactive moiety.
An opportunity therefore remains to develop new polymer-bioactive moiety conjugates which address or ameliorate one or more disadvantages or shortcomings associated with existing materials and/or their method of manufacture, or to at least provide a useful alternative to such materials and their method of manufacture.